S-34-01

Genetic risk factors as possible causes of the variation in European suicide rates

A. Marusic. Institute of Public Health of Ljubljana, Slovenia

Objective: The current state of knowledge of genetic predisposition towards the suicidal behaviour allows for a question whether genetic risk factors account for the variation in suicide rates through time and space. Accordingly, the lecture will attempt to tackle the genetics behind suicidal behaviour from the perspective of the populational genetics. First, suicide rates variability of suicide rates across Europe is discussed. This is followed by a brief discussion of the J curve (on a map of Europe, the countries with a higher suicide rate form a so-called J curve, which starts in Finland and extends down to Slovenia), which maps on to the second principal component identified for European gene distribution, representing the ancestral adaptation to cold climates and the Uralic language dispersion. Furthermore, we will discuss whether the group of people living within the J-curve could share genes, which may not tolerate well excessive amounts alcohol, the combination of which is more likely to end in suicidal behaviour. Further along we list possible ways in which suicidal behaviour could have been selected for genetically in populations and identify those specific populations in which it may have appeared. Finally, we point at other locations in the world where a similar interplay of genes and environment has probably occurred, Greenland being the best example of the malignant interaction of alcohol consumption and the trait-like characteristics, which might constitute the vulnerability to suicidal behaviour.

S-34-02

In vivo functional neuro-imaging provides new insights into the suicidal brain

C. van Heeringen, K. Bernagie, M. Vervaet, K. Audenaert. University Hospital Gent, Dept, Gent, Belgium

Objective: This review of neuro-imaging findings in attempted suicide patients, depressed non-suicidal patients, and healthy controls will show that, from a neuro-anatomical point of view, there is now increasing insight in the role of prefrontal-subcortical circuits in the development of suicidal behaviour through their involvement in the modulation of trait-dependent cognitive and/or emotional characteristics

Results: From a neurobiologieal point of view, the role of serotonin in particular is elucidated through receptor binding studies and through the study of correlations between receptor binding indices and psychopathological characteristics.

Conclusion: Taken together with the results of biological, neuropsychological and cognitive psychological challenge studies, these findings provide new insights in the suicidal brain.

S-34-03

Serotonergic genes influence suicidal behaviour

A. Malafosse. Division de Neuropsychiatrie, Ch~ne-Bourg, Switzerland

Objective: The involvement of genetic risk factors and of interaction between genes and environment in suicidal behaviour is supported by family, twin, and adoption studies. Several lines of evidence indicate that disturbances of the central serotonin system are involved in the neurobiology of suicide, possibly by modulating a restraint function in which the ventromedial prefrontal cortex seems to play an important role. Accordingly, several molecular genetic studies of serotonin-related genes have been published. Promising results have been obtained with the serotonin transporter (5-HTF) gene. The 5-HTT plays a crucial role in maintaining presynaptic homeostasis in several ways. A recent recta-analysis provides significant evidence supporting the association between the S allele of a functional 5-HTT promoter polymorphism and suicidal behaviour, also with violent suicide. Interestingly, it has recently been shown that the 5-HTI" gene interacts with life events to predict suicidality: the effect of life events on subjects reports of suicide behaviour was stronger among individuals carrying an S allele than among L/L homozygotes. The other widely studied gene is that coding for tryptophan hydroxylase (TPH). TPH is the ratelimiting enzyme in the synthesis of serotonin. Two different genes code for TPH: TPH1 and TPH2. Two recta-analyses of association studies between the TPH1 A218C polymorphism and suicidal behaviour in Caucasian populations clearly suggest an association between the A allele and suicidal behaviour. TPH2 gene has recently been associated with suicide but this result is not confirmed by recent studies. Studies of other serotonin-related genes are so far inconclusive.

S-34-04

Aggression-related genes in suicidal behavior: An intermediate phenotype strategy in the search for genetic susceptibility factors

I. Giegling, I. Dietrich, A. M. Hartmann, H. J. Möller, D. Rujescu. University of Munich Dept. of Psychiatry, Munich, Germany

Risk of suicide-related behavior is supposed to be determined by a complex interplay of sociocultural factors, traumatic life experiences, psychiatric history, personality traits, and genetic vulnerability. This view is supported by adoption and family studies indicating that suicidal acts have a genetic contribution that is independent of the heritability of Axis I and II psychopathology. The heritability for serious suicide attempts was estimated to be 55%. Neurobiological studies have shown that serotonergic dysfunction is implicated in suicidal behaviors. These findings stimulated the investigation of variations in serotonergic genes in this context. We have initiated a large scale case control genetic association study which comprises of 250 suicide attempters and 600 healthy volunteers and investigated the role of a comprehensive set of serotonergic candidate genes in this behavior. We will present new data on a comprehensive set of serotonergic candidate genes. Since both, aggression related traits and serotonergic activity are partially heritable and correlate inversely, variations in genes of the serotonergic system might then, to some extent, account for variations in aggression-related behavior. Thus, we also investigated the relationship between serotonergic genes and anger, as a subtype of aggression-related behavior.